Pembrolizumab (pembro) plus enzalutamide (enza) for enza-resistant metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-199 cohorts 4-5.
Julie N. Graff, Emmanuel S. Antonarakis, Christopher Hoimes, Scott T. Tagawa, Clara Hwang, Deepak Kilari, AJ ten Tije, Aurelius Omlin, Raymond S. McDermott, Ulka N. Vaishampayan, Anthony Elliott, Helen Wu, Jeri Kim, Charles Schloss, Johann S. de Bono
Abstract
15 Background: KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study. Cohort (C)4 (RECIST-measurable disease) and C5 (bone-predominant disease) consist of chemotherapy-naive patients (pts) with mCRPC treated with enza + pembro after progression with enza. Results for C4 and C5 presented. Methods: Pts with or without prior abiraterone had clinically meaningful response/benefit to enza followed by disease progression. Pts received pembro 200 mg Q3W with continuation of enza for up to 35 cycles or until progression/intolerable toxicity. Primary end point: ORR, blinded independent central review (C4). Secondary end points: DCR, PSA response rate (≥50% reduction), rPFS, OS, and safety (C4, C5); DOR (C4). Results: Of 126 pts (C4, 81; C5, 45), 107 discontinued, primarily due to progression. Median follow-up: 13.7 mo (C4, 11.8; C5, 18.6). ORR (95% CI) for pts with measurable disease was 12% (6-22) in C4; DCR for all pts: 51% (39-62) in C4 and 51% (36-66) in C5 (Table). Any grade/grade 3-5 treatment-related AEs occurred in 75%/26% pts in C4 and 69%/24% in C5. Two pts in C4 died of immune-related AEs (Miller Fisher syndrome and myasthenia gravis). Incidence of any grade/grade 3-4 rash (regardless of treatment relatedness) was higher than previously reported for individual agents (33%/6%). All except one pt (grade 3 treated with IV steroids) were treated with oral/topical steroids or had no intervention. Conclusions: Addition of pembro to enza following enza resistance showed modest antitumor activity in pts with RECIST-measurable and bone-predominant mCRPC. Combination had manageable safety and is being evaluated in a phase 3 trial. Clinical trial information: NCT02787005. [Table: see text]